Aralkylation of guanosine with para-substituted styrene oxides.
To probe mechanisms of nucleoside aralkylation, product distributions and product stereochemistries were determined in reactions of optically active p-methyl- and p-bromostyrene oxide with guanosine. The proportion of 7-, N2-, and O6-substituted guanosine products was approximately 0.32:0.62:0.06 in neutral, aqueous reactions with the (R)-p-methylstyrene oxide and approximately 0.85: 0.09:0.04 in reactions with the (R)-p-bromostyrene oxide. The exocyclic positions opened the epoxide at the alpha-carbon. Epoxide ring opening by the nitrogen at the 7-position showed little preference for the alpha- or beta-carbons in reactions with p-methylstyrene oxide. However, the p-bromostyrene oxide favored reaction at the beta-carbon almost 4-fold over reaction at the alpha-carbon. Almost total inversion of stereochemistry was found to occur in reactions at the 7-position. In contrast, the ratio of inversion to retention of configuration in N2- and O6-substituted products was approximately 2:1 and approximately 1:1 for reactions with the p-methylstyrene oxide and approximately 6:1 and approximately 3:1 for reactions with p-bromostyrene oxide, respectively. These experiments suggest that an SN2 mechanism is in effect with reactions at the 7-position, whereas substrates of an increasingly ionic nature are involved in reactions at the N2- and O6-positions, respectively.
Barlow
T
T
Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Dipple
A
A
D002273:Carcinogens / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D006151:Guanosine / Q000737:chemistry*; D009153:Mutagens / Q000737:chemistry*
D002273:Carcinogens; D018736:DNA Adducts; D004852:Epoxy Compounds; D009153:Mutagens; D006151:Guanosine; C013690:styrene oxide